Multiple Sclerosis (MS) is a major neurological disease affecting over 400,000 Americans and 2.5 million worldwide. Pathological studies suggest these numbers should be doubled. In addition, the number of people with MS is increasing, especially in women. The disease has a devastating impact, and commonly produces disability in the motor, cognitive and vocational spheres. It is the most common non-traumatic central nervous system (CNS) disease of young adults, hitting them in what should be their most productive years. This causes personal hardship and loss to our workforce and the economy. Although there is no cure, there are FDA approved drugs that can prevent further deterioration of patients. They are most effective when given as soon as the diagnosis can be made. The bottleneck is how to make that diagnosis. The current study is designed to establish a diagnostic test for early MS. This would be a landmark achievement because no such test currently exists. Now diagnosis is based on history, examination, and a combination of suggestive but not conclusive laboratory testing. The diagnosis is typically delayed several years. A diagnostic test for early MS would be of critical importance for patients with this disease by allowing immediate institution of therapy. We will follow up on our recently published studies indicating protein biomarkers are present at this stage of the disease. Identification of such biomarkers is the basis of a diagnostic test. We will employ advanced proteomic techniques to accomplish this. Our team has the expertise and the necessary samples to do achieve this.This project provides the critical and necessary first step in identifying biomarkers for first-attack MS. Eventually the markers will provide objective diagnostic criteria and a possibly a response-monitoring tool for therapeutic trials. A reliable, objective diagnostic test fr MS will reduce disability and suffering including that for families, health care and lost productivity costs. We have the relevant samples, personnel to start immediately.